Coronavirus COVID-19 Vaccines

Updated: July 15, 2020

COVID-19 Vaccines in Development

  • Multiple vaccines are under development: approximately 23 are in clinical trials (Table 1) and 140 in preclinical evaluation.[1]
  • For overview of trial design, see Clinical Trial Phases and Definitions
  • Among those with the greatest potential for speed are DNA- and RNA-based platforms, followed by those for developing recombinant-subunit vaccines.
  • RNA and DNA vaccines can be made quickly because they require no culture or fermentation, instead using synthetic processes.

Recent updates:

  • Moderna mRNA-1273 vaccine Phase I study published in New England Journal of Medicine.[2] Forty-five adults age 18–55 were tested with one of three dose levels given as 2 vaccinations 28 days apart. All subjects produced antibodies and neutralizing activity on par with natural infection. Mild-moderate side effects were common.
  • Novavax receives U.S. Warp Speed funding for NVX-CoV2373 protein-based vaccine development and clinical trials.[3]
  • BioNTech and Pfizer report success of mRNA-based vaccine BNT162b1 in Phase 1/2 trial.[4]
  • INOVIO reports success of DNA-based vaccine INO-4800 in Phase 1 trial.[5]
  • CanSino Biologics received Military Specially-needed Drug Approval (軍隊特需藥品批件) for non-replicating adenovirus vaccine Ad5-nCoV for use in the Chinese military.[6]

COVID-19 Vaccines in Clinical Trials

Table 1. COVID-19 Candidate Vaccines Undergoing Clinical Evaluation

Platform

Type

Developer

Current stage

Non-Replicating Viral Vector

Weakened adenovirus (ChAdOx1-S; AZD1222)

Warp SpeedUniversity of Oxford/ AstraZeneca

Phase 3 ISRCTN89951424

Phase2b/3 NCT04400838

Phase 1/2 PACTR202006922165132; 2020-001072-15

Inactivated

Inactivated + alum (CoronaVac; formerly PiCoVacc)

Sinovac

Phase 3 NCT04456595

Phase 1/2 NCT04383574 ; NCT04352608; Results in Science[7]

Non-Replicating Viral Vector

Adenovirus Type 5 Vector (Ad5-nCoV)

CanSino Biological Inc./ Beijing Institute of Biotechnology

Phase 2 NCT04341389

Phase 1 NCT04313127; Results in Lancet[8]

RNA

LNP-encapsulated mRNA (mRNA-1273)

Warp SpeedModerna/ NIAID

Phase 3 NCT04470427

Phase 2 NCT04405076

Phase 1 NCT04283461; Results in NEJM[2]

DNA

DNA plasmid vaccine with electroporation (INO-4800)

Inovio Pharmaceuticals / International Vaccine Institute

Phase 1/2 NCT04336410; NCT04447781

Inactivated

Inactivated

Wuhan Institute of Biological Products/ Sinopharm

Phase 1/2 ChiCTR2000031809

Inactivated

Inactivated (BBIBP-CorV)

Beijing Institute of Biological Products/ Sinopharm

Phase 1/2 ChiCTR2000032459

Protein Subunit

Recombinant SARS CoV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M (NVX-CoV2373)

Warp SpeedNovavax

Phase 1/2 NCT04368988

RNA

3 LNP-mRNAs (BNT162)

Warp SpeedBioNTech/ Fosun Pharma/ Pfizer

Phase 1/2 2020-001038-36 NCT04368728

Inactivated

Whole-Virion Inactivated

Bharat Biotech

Phase 1/2 CTRI/2020/07/026300

Inactivated

Inactivated

Institute of Medical Biology, Chinese Academy of Medical Sciences

Phase 1 NCT04412538

DNA

DNA Vaccine (GX-19)

Genexine Consortium

Phase 1 NCT04445389

DNA

DNA plasmid vaccine

Cadila Healthcare Limited

Phase 1/2 CTRI/2020/07/026352

DNA

DNA plasmid vaccine + Adjuvant

Osaka University/ AnGes/ Takara Bio

Phase 1 JapicCTI-205328

Non-Replicating Viral Vector

Adenovirus-based (Gam-COVID-Vac)

Gamaleya Research Institute

Phase 1 NCT04436471 NCT04437875

Protein Subunit

Native like Trimeric subunit Spike Protein vaccine (SCB-2019)

Clover Biopharmaceuticals Inc./ GSK/ Dynavax

Phase 1 NCT04437875

Protein Subunit

Adjuvanted recombinant protein (RBD-Dimer)

Anhui Zhifei Longcom Biopharmaceutical/ Institute of Microbiology, Chinese Academy of Sciences

Phase 1 NCT04445194

Protein Subunit

Recombinant spike protein with Advax™ adjuvant

Vaxine Pty Ltd/ Medytox

Phase 1 NCT04453852

Protein Subunit

Molecular clamp stabilized Spike protein with MF59 adjuvant

University of Queensland/ CSL/ Seqirus

Phase 1 ACTRN12620000674932p

RNA

LNP-nCoVsaRNA

Imperial College London

Phase 1 ISRCTN17072692

RNA

mRNA

Curevac

Phase 1 NCT04449276

RNA

mRNA

People’s Liberation Army (PLA) Academy of Military Sciences/Walvax Biotech

Phase 1 ChiCTR2000034112

VLP

Plant-derived VLP

Medicago Inc./ Université Laval

Phase 1 NCT04450004

Adapted from Draft landscape of COVID-19 candidate vaccines. WHO. 14 July 2020.[1]

LNP = lipid nanoparticle; RBD = receptor-binding domain; mRNA = messenger RNA; VLP = virus-like particles

Warp SpeedRecipient of U.S. Operation Warp Speed Funding[9],[10]

COVID-19 Vaccine Trial Phases and Definitions

Preclinical Testing

Vaccine given to animals such as mice or monkeys to see if it produces an immune response.

Phase I

Vaccine given to a small number of people to test safety and dosage as well as to confirm that it stimulates the immune system.

Phase II

Vaccine given to hundreds of people split into different age or risk groups groups to see if the vaccine acts differently in them. These trials further test the vaccine’s safety and ability to stimulate the immune system.

Phase III

Vaccine given to thousands of people and wait to see how many become infected, compared with volunteers who received a placebo. These trials can determine if the vaccine protects against the coronavirus.

Approval

Regulators in each country review the trial results and decide whether to approve the vaccine or not. During a public health emergency, a vaccine may receive Emergency Use Authorization (EUA) before getting formal approval.

Warp Speed

The U.S. government’s Operation Warp Speed program is expected to name five or more vaccine projects to receive billions of dollars in federal funding before there’s proof that the vaccines work.

Combined Phases

Some coronavirus vaccines are now in combined phase trials to speed evalutation. For instance, many Phase I/II trials are underway to test a vaccine for the first time on hundreds of people.

COVID-19 ClinicalTrials.gov Trials

References

  1. Draft landscape of COVID-19 candidate vaccine. World Health Organization. July 6, 2020. [https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candid...]
  2. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020.  [PMID:32663912]
  3. U.S. Will Pay $1.6 Billion to Novavax for Coronavirus Vaccine. New York Times. July 7, 2020. [https://www.nytimes.com/2020/07/07/health/novavax-coronavirus-vaccine-warp...]
  4. Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. medRxiv 2020.06.30.20142570; doi: https://doi.org/10.1101/2020.06.30.20142570
  5. INOVIO Announces Positive Interim Phase 1 Data For INO-4800 Vaccine for COVID-19. Press Release. June 30, 2020. http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-Annou...
  6. Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Received Military Specially-needed Drug Approval. Hong Kong Stock Exchange Filing. June 25, 2020. https://www1.hkexnews.hk/listedco/listconews/sehk/2020/0629/2020062900123....
  7. Gao Q, Bao L, Mao H, et al. Rapid development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020.  [PMID:32376603]
  8. Zhu FC, Li YH, Guan XH, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020;395(10240):1845-1854.  [PMID:32450106]
  9. Fact sheet: explaining Operation Warp Speed. US Department of Health & Human Services. Published June 16, 2020. Accessed July 9, 2020. [https://www.hhs.gov/about/news/2020/06/16/fact-sheet-explaining-operation-warp-speed.html]
  10. O'Callaghan KP, Blatz AM, Offit PA. Developing a SARS-CoV-2 Vaccine at Warp Speed. JAMA. 2020.  [PMID:32628244]
  11. Deming ME, Michael NL, Robb M, et al. Accelerating Development of SARS-CoV-2 Vaccines - The Role for Controlled Human Infection Models. N Engl J Med. 2020.  [PMID:32610006]
  12. Graham BS. Rapid COVID-19 vaccine development. Science. 2020;368(6494):945-946.  [PMID:32385100]
  13. Lurie N, Saville M, Hatchett R, et al. Developing Covid-19 Vaccines at Pandemic Speed. N Engl J Med. 2020;382(21):1969-1973.  [PMID:32227757]
Last updated: July 15, 2020